Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Claims
Claims 1, 5, 7-8, 12-14, 34, 37-39, 67-72, and 74-76 are pending in the instant application.
Claims 2-4, 6, 9-11, 15-33, 35-36, 40-66, 73, and 77-79 have been canceled.
Election/Restrictions
This action is in response to an election from a restriction requirement filed on May 5th, 2026. There are 20 claims pending and 16 claims under consideration. Claims 34, 39, and 75-76 have been withdrawn as claims not drawn to the elected invention. This is the first action on the merits. The present invention relates to a compound of Formula I as recited at instant Claim 1.
Applicant’s election with traverse of Group I, Claims 1, 5, 7-8, 12-14, 37-38, 67-72, and 74 and a species election of a single species of a compound of Formula I as compound I-86 in the reply received July 30th, 2026 is acknowledged.
The traversal is on the grounds that no undue burden exists to simultaneously search the subject matter of Groups I through III. Applicant asserts that the compounds of Formula I-A defined by claims 34 and 39 are a subset of the compounds of Formula I defined by the independent claim 1, and that because Group III is directed to a method of treatment using the compound of Claim 1, no undue burden to examine Group III exists since these compounds will have already been examined.
This traversal is not found persuasive.
As noted in the restriction requirement mailed May 5th, 2026, unity of invention is lacking because there is no substantial structural element that is common to all compounds of Formula I. Because no common structure is present and all alternatives do not belong to a recognized class of chemical compounds, no special technical feature exists such that these groups of inventions relate to a single inventive concept under PCT Rule 13.1.
Therefore, the restriction is considered proper and thus made FINAL.
The elected species of compound I-86 was found to be free of the prior art. Thus, examination was extended to all compounds of Formula I.
Domestic Benefit
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 120 as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 63/251,712, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
The full scope of Claims 1, 5, 7-8, 12-14, 37-38, 67-72, and 74 are not supported by the prior-filed application. Many of the compounds embraced by instant Claim 1 and disclosed in the instant specification do not find support in the prior-filed application. For example, instant Claim 72 is drawn to a compound in Table 1, 2, 3, or 4, or a pharmaceutically acceptable salt thereof. Compounds II-181 through II-193 are not disclosed in the prior-filed application. Therefore, the instant application is drawn to a broader scope of compounds than is disclosed in the prior-filed application.
To this end, elected Claims 1, 5, 7-8, 12-14, 37-38, 67-72, and 74 do not receive the benefit of the filing date of Application No. 63/251,712.
The instant application is a National Stage entry of PCT/US2022/045637, and will be evaluated with an effective filing date of October 4th, 2022.
Information Disclosure Statement
The Information Disclosure Statements received March 20th, 2025, September 3rd, 2025, and July 30th, 2026 have been fully considered by the examiner, except where marked with a strikethrough.
Specification
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any of the errors of which Applicant may become aware of in the specification.
Claim Objections
Claims 14 and 72 are objected to because of the following informalities:
Claim 14 does not end with a period. Per MPEP 608.01(m), “Each claim begins with a capital letter and ends with a period.”
Claim 72 improperly references Tables 1, 2, 3, and 4. Per MPEP 2173.05(s), “Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).”
Appropriate correction is required.
Claim Rejections – Improper Markush Grouping
Claims 1, 5, 7-8, 12-14, 37-38, 67-72, and 74 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of compounds represented by Formula I is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
The Markush grouping is directed to compounds of Formula I. Formula I is:
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The EPL and TPL moieties encompass a very broad scope of distinct chemical moieties defined by ability to bind to an effector protein selected from GSPT1, Cyclin K, RBM23, RBM39, IKZF1, IKZF3, PLK1, CDK4, or CK1alpha in the case of the EPL moiety or the ability to bind a target protein selected from KRAS, HER2, BTK, EGFR, androgen receptor protein, estrogen receptor protein, ALK, IDH1, FLT3, FGFR1, FGFR2, FGFR3, ERK1, ERK2, FGR, HER3, or HER4 in the case of the TPL moiety. This encompasses a range of moieties with distinct functions determined by the proteins in which these moieties bind. Further, these moieties encompass a breadth of structures that include distinct ring systems that are not obvious variants of each other. Further, these moieties include a broad range of entities known presently, but also cover any number of chemical moieties discovered years from now that meet the limitation of binding to any of these proteins. Additionally, L1 and L2 may both either be a bond or a linker-containing moiety. As defined by the instant specification, the linker further encompasses numerous distinct chemical moieties readily envisaged by a person having ordinary skill in the art.
The result is a group of compounds that include distinct ring systems that share no significant structural similarity. This grouping includes compounds that are not obvious variants of each other. To this end, a comparison of compound I-1 from Table 1 and compound III-20 from Table 3, disclosed at Pages 147 and 250 of the instant specification, respectively demonstrates compounds of Formula I lacking significant structural similarity that are not obvious variants of each other:
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244
542
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321
540
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To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 5, 7-8, 12-14, 37-38, 67-71, and 74 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a compound of Formula I in which the variables are defined as follows:
R1, R2, R3, and R4 are independently H, halo, or methyl.
R5 is H.
EPL is selected from a moiety that is:
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89
408
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, wherein the C1-4 alkylene is methylene, R1a is hydrogen, R2a and R3a are each hydrogen, R4a is halo or methyl, and n is 2;
Or a moiety selected from the group consisting of
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96
416
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,
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101
427
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,
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94
437
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,
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107
437
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,
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81
457
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,
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102
437
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,
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103
404
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, or
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107
486
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, wherein the C1-4 alkylene is methylene, R1a is hydrogen, R2a and R3a are each hydrogen, R4a and R5a are each halogen, methyl, trifluoromethyl, hydroxyl, nitro, or methoxy, X1a is methylene, m is 0 or 1, and n is 0, 1, or 2;
Or EPL is selected from one of the following moieties:
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170
116
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,
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77
193
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,
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217
127
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, or
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211
122
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;
the TPL moiety is selected from the following:
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194
205
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,
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187
162
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,
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431
625
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,
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444
555
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,
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180
554
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,
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237
319
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,
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218
354
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,
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219
168
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,
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661
413
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,
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238
489
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,
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214
160
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,
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188
161
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,
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203
176
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197
160
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,
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234
556
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,
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318
541
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,
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460
489
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489
474
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,
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211
229
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382
443
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,
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378
462
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136
406
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,
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177
481
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381
494
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253
528
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,
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111
229
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,
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126
263
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489
588
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150
241
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,
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167
286
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,
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221
576
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,
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250
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L1 is a bond, **-linker-O-, or **linker-N(R5) wherein the linker is C1-2 alkyl, -C(O)O-NH-C1-4-alkyl, or C(O)OC1-4 alkyl;
L2 is a bond or a linker wherein the linker is N(Me)-C1-4-alkyl-O-, C1-4-alkyl-O, C1-4-alkyl-NH-, C1-4-alkyl-N(Me)-C1-4-alkyl-N(Me)-C1-4alkyl, or C1-4 alkyl.
The instant specification does not reasonably provide enablement for compounds of Formula I in which these variables are otherwise defined. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Pursuant to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required: (1) The breadth of the claims, (2) The nature of the invention, (3) The state of the prior art, (4) The level of one of ordinary skill, (5) The level of predictability in the art, (6) The amount of direction provided by the inventor, (7) The existence of working examples and (8) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Nature of the invention:
The invention is drawn to compounds of Formula I as recited at instant Claim 1.
Breadth of the invention:
The scope of the claimed invention is very broad. The invention is drawn to compounds of the formula:
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allowing for myriad combinations of the variables recited thereof. Further, with respect to the EPL moiety, TPL moiety, and recitation of linkers in variables L1 and L2, the specification provides non-limiting examples demonstrating a plethora of distinct moieties that are not obvious variants of each other that can be assigned to each respective variable interchangeably. Especially with respect to the EPL and TPL moieties, these variables are not limited to a specific structure or group of structures, but rather limited by recitation of function of chemical moieties. This broad recitation includes moieties not only known presently to bind to an effector protein selected from GSPT1, Cyclin K, RBM23, RBM39, IKZF1, IKZF3, PLK1, CDK4, or CK1alpha in the case of the EPL moiety, and moieties that bind to a target protein selected from KRAS, HER2, BTK, EGFR, androgen receptor protein, estrogen receptor protein, ALK, IDH1, FLT3, FGFR1, FGFR4, FGFR2, FGFR3, ERK1, ERK2, FGR, HER3, or HER4 in the case of the TPL moiety. In addition to the exemplary moieties provided in the instant specification representing a plethora of distinct chemical moieties that are not obvious variants of each other, this limitation covers all moieties that bind any of these proteins, both known presently, or those that are discovered years from now to bind one of these proteins. Can Applicant simply “reach through” and obtain patent protection over the inclusion of chemical moieties that are either yet to be discovered, or moieties presently known that are later discovered to bind one of the recited proteins?
State of the prior art and predictability in the art:
The invention is directed toward medicine and is therefore physiological in nature. It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F. 2d 833, 839, 166, USPQ 18, 24 (CCPA 1970).
In terms of the law, MPEP 2107.03 states “evidence of pharmacological or other biological activity of a compound will be relevant to an asserted therapeutic use if there is reasonable correlation between the activity in question and the asserted utility. Cross v. Iizuka, 753 F. 2d 1040, 224 USPQ 739 (Fed. Cir. 1985); In re Jolles, 628 F. 2d 1322, 206 USPQ 885 (CCPA 1980); Nelson v. Bowler, 626 F. 2d 853, 206 USPQ 881 (CCPA 1980).” If correlation is lacking, it cannot be relied upon, Ex parte Powers, 220 USPQ 924; Rey-Bellet and Spiegelberg v. Engelhardt v. Schindler, 181 USPQ 453; Knapp v. Anderson, 177 USPQ 688. Indeed, the correlation must have been established “at the time the tests were performed”, Hoffman v. Klaus, 9 USPQ2d 1657.
Level of ordinary skill in the art:
An ordinary artisan in the area of drug development would have experience in synthesizing chemical compounds for particular activities. The synthesis of new drug candidates, while complex, is routine in the art. The process of finding new drugs that have in vitro activity against a particular biological target (i.e., receptor, enzyme, etc.) is well known. Additionally, while high throughput screening assays can be employed, developing a therapeutic method, as claimed, prior to synthesizing and testing compounds is generally not well-known or routine, given the complexity of certain biological systems.
The amount of direction provided and working examples:
Beginning at Page 147 of the instant specification, Applicant has provided numerous examples of compounds in Tables 1, 1-A, 2, 2-A, 3, and 4 that read on the limitations as recited at Claim 1 with sufficient guidance for how to make and use. However, this disclosure is not sufficient to allow extrapolation of the limited examples to enable the scope of the compounds instantly claimed. Applicant has provided no working examples of any compounds, compositions, or pharmaceutically acceptable salts thereof in which R1, R2, R3, R4, R5, EPL, TPL, L1, or L2 were not defined as mentioned above in the instant application.
Within the specification, “specific operative embodiments or examples of the invention must be set forth. Examples and description should be of sufficient scope as to justify the scope of the claims.” Markush claims must be provided with support in the disclosure for each member of the Markush group. Where the constitution and formula of a chemical compound is stated only as a probability or speculation, the disclosure is not sufficient to support claims identifying the compound by such composition or formula. See MPEP 608.01(p).
MPEP § 2164.01 (a) states, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).” That conclusion is clearly justified here that Applicant is not enabled for making these compounds.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 5, 7-8, 12-14, 37-39, 67-72, and 74 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 is rendered indefinite due to the recitation of the limitation “EPL is a moiety that binds to an effector protein selected from GSPT1, Cyclin K, RBM23, RBM39, IKZF1, IKZF3, PLK1, CDK4, or CK1alpha”. Based on the instant disclosure, a person having ordinary skill in the art would not be able to readily ascertain the metes and bounds of this limitation. While the specification provides exemplary embodiments of the EPL moiety, this is not sufficient to clearly establish the metes and bounds of this limitation, as many distinct moieties, either presently known, or those later discovered can read on this limitation. For the same reason, the limitation “EPL is a moiety that binds to GSPT1” renders Claim 7 indefinite.
Claim 1 is rendered indefinite due to the recitation of the limitation “TPL is a moiety that binds to a target protein selected from KRAS, HER2, BTK, EGFR, androgen receptor protein, estrogen receptor protein, ALK, IDH1, FLT3, FGFR1, FGFR4, FGFR2, FGFR3, ERK1, ERK2, FGR, HER3, or HER4”. Based on the instant disclosure, a person having ordinary skill in the art would not be able to readily ascertain the metes and bounds of this limitation. While the specification provides exemplary embodiments of the TPL moiety, this is not sufficient to clearly establish the metes and bounds of this limitation, as many distinct moieties, either presently known, or those later discovered can read on this limitation.
Claim 1 is indefinite for the limitations “L1 is… **linker-O-, **-linker-N(R5)-“ and “L2 is… a linker”. A person having ordinary skill in the art would not readily be able to ascertain the metes and bounds of the “linker” limitation based on the instant disclosure. While several non-limiting examples of a linker are provided, a person having ordinary skill in the art would readily be able to envisage many more distinct chemical moieties that read on this broad limitation.
Dependent Claims 5, 7-8, 12-14, 37-39, 67-72, and 74 do not resolve this indefiniteness, and therefore are also rendered indefinite.
Conclusion
Claims 1, 5, 7-8, 12-14, 37-39, 67-72, and 74 are rejected.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DANIEL JOHN BURKETT whose telephone number is (703)756-5390. The examiner can normally be reached Monday - Friday.
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/D.J.B./Examiner, Art Unit 1624
/BRENDA L COLEMAN/Primary Examiner, Art Unit 1624
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